Urinary androgens and breast cancer risk: results from a long-term prospective study based in Guernsey

Between 1961 and 1967 a cohort of over 5000 women volunteered for a prospec tive study to determine the relationship between the urinary androgen metab olites, androsterone (A) and aetiocholanolone (E), and risk of breast cance r. During the first 10 years of the study the concentration of urinary A an d E was determined in 1887 of the urine specimens. In 1971 we reported that subnormal amounts of urinary A and E were associated with a significantly increased risk of breast cancer. The cohort has been followed regularly dur ing the 37 years since inception of the study and, by May 1998, 248 women h ad been diagnosed with breast cancer. Urinary androgen metabolites had been measured in 116 of these cases. Analysis of these data confirmed that wome n diagnosed in the first decade of the study were more likely to have low l evels of urinary androgen metabolites. In the following decades, however, t hose who developed breast cancer were more likely to have manifested an inc reased A and E excretion. The reversal in the relationship between androgen metabolite excretion and risk suggests that age, or probably more importan tly, menopausal status at diagnosis is an important modifying factor, Dicho tomizing at age 50 it was found that in the younger age group (predominantl y premenopausal) the rate ratios in the lowest tertile of A or E excretion were two- to threefold greater than for those in the highest tertile (chi(1 )(2) = 3.57; P = 0.06: chi(1)(2) = 4.70; P = 0.03 for A and E respectively) . In contrast, in the older age group comprising predominantly post-menopau sal women, the rate ratios associated with the lowest tertile of A or E wer e half that of those in the highest tertile (chi(1)(2) = 4.10; P = 0.04; ch i(1)(2) = 8.72; P = 0.003 for A and E respectively). This suggests that the re may be different endocrine promotional factors for pre-and post-menopaus al breast cancer. Hormonal risk factors may vary during the lifetime of an individual woman and this may have profound consequences for prevention str ategies. (C) 2000 Cancer Research Campaign.